Very small embryonic-like (VSELs) and ovarian (OSCs) stem cells are located in adult mammalian ovary surface epithelium (OSE). OSCs can expand long-term and differentiate into oocyte-like structures in vitro and have resulted in birth of fertile pups. Lineage tracing studies have provided evidence to suggest OSCs differentiation into oocytes in vivo. But how these stem cells function under normal physiological conditions has not yet been well worked out. Besides studying STRA-8 and SCP-3 expression in enzymatically isolated OSE cells smears, mice were injected BrdU to track mitosis, meiosis and follicle assembly. H&E stained OSE cells during late diestrus and proestrus showed VSELs undergoing asymmetrical cell divisions to give rise to slightly bigger OSCs which in turn underwent symmetrical cell divisions followed by clonal expansion (rapid expansion with incomplete cytokinesis) during early estrus to form germ cell nests (GCN). OCT-4, SSEA-1, MVH and DAZL positive cells in GCN expressed Erα, Erβ and FSHR, were interconnected by ring canals (TEX-14), showed mitochondrial aggregation (Cytochrome C) and Balbiani Body (TRAL). Apoptosis in ‘nurse’ cells was marked by PARP and putative oocytes were clearly visualized. BrdU was detected in cells undergoing mitosis/meiosis and also in an oocyte of secondary follicle. FACS sorted, green fluorescent protein (GFP) positive VSELs upon transplantation resulted in GFP positive GCN suggesting crucial role for VSELs in adult ovaries. Results suggest that various events described during oogenesis and follicle assembly in fetal ovaries are recapitulated on regular basis in adult ovary and result in the formation of follicles.

Graphic abstract

中文翻译：

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成年小鼠卵巢中的干细胞在发情周期中定期形成生殖细胞巢、进行减数分裂、新卵子发生和卵泡组装

非常小的胚胎样 (VSEL) 和卵巢 (OSC) 干细胞位于成年哺乳动物卵巢表面上皮 (OSE) 中。OSCs 可以长期扩张并在体外分化成卵母细胞样结构，并导致生育幼崽的诞生。谱系追踪研究提供了证据表明 OSC 在体内分化为卵母细胞。但这些干细胞如何在正常生理条件下发挥作用尚未得到很好的研究。除了研究酶促分离的 OSE 细胞涂片中 STRA-8 和 SCP-3 的表达外，还向小鼠注射 BrdU 以跟踪有丝分裂、减数分裂和卵泡组装。H＆在发情后期和发情前期，E 染色的 OSE 细胞显示 VSEL 经历不对称细胞分裂以产生稍大的 OSC，而后者又经历对称细胞分裂，然后在早期发情期进行克隆扩增（不完全胞质分裂的快速扩增），形成生殖细胞巢（GCN） ）。GCN中OCT-4、SSEA-1、MVH和DAZL阳性细胞表达Erα、Erβ和FSHR，通过环管（TEX-14）相互连接，显示线粒体聚集（细胞色素C）和巴尔比亚尼体（TRAL）。“护士”细胞的凋亡由 PARP 标记，推定的卵母细胞清晰可见。在经历有丝分裂/减数分裂的细胞以及次级卵泡的卵母细胞中检测到 BrdU。FACS 排序，移植后的绿色荧光蛋白 (GFP) 阳性 VSEL 导致 GFP 阳性 GCN，表明 VSEL 在成人卵巢中的关键作用。结果表明，在胎儿卵巢的卵子发生和卵泡组装过程中描述的各种事件在成人卵巢中定期重现，并导致卵泡的形成。

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